Medical Specialties Commons^™

Green Solvent Mediated Extraction Of Micro- And Nano-Plastic Particles From Water, Jameson R. Hunter, Qi Qiao, Yuxuan Zhang, Qing Shao, Czarena L. Crofcheck, Jian Shi

Markey Cancer Center Faculty Publications

The production of plastic and the amount of waste plastic that enters the ecosystem increases every year. Synthetic plastics gradually break down into particles on the micro‑ and nano‑scale in the environment. The micro‑ and nano‑plastics pose a significant ecological threat by transporting toxic chemicals and causing inflammation and cellular damage when ingested; however, removal of those particles from water is challenging using conventional separation methods. Deep eutectic solvents (DES), a new class of solvents composed of hydrogen bond donors and acceptors, have been proposed as a cheaper alternative to ionic liquids. Hydrophobic DES derived from natural compounds (NADES) show …

Identifying And Sharing Per-And Polyfluoroalkyl Substances Hot-Spot Areas And Exposures In Drinking Water, Sweta Ojha, P. Travis Thompson, Christian D. Powell, Hunter N. B. Moseley, Kelly G. Pennell

Markey Cancer Center Faculty Publications

Exposure to per- and polyfluoroalkyl substances (PFAS) in drinking water is widely recognized as a public health concern. Decision-makers who are responsible for managing PFAS drinking water risks lack the tools to acquire the information they need. In response to this need, we provide a detailed description of a Kentucky dataset that allows decision-makers to visualize potential hot-spot areas and evaluate drinking water systems that may be susceptible to PFAS contamination. The dataset includes information extracted from publicly available sources to create five different maps in ArcGIS Online and highlights potential sources of PFAS contamination in the environment in relation …

Noncovalent Interactions That Tune The Reactivities Of The Flavins In Bifurcating Electron Transferring Flavoprotein, María González-Viegas, Rajiv K. Kar, Anne-Frances Miller, Maria-Andrea Mroginski

Markey Cancer Center Faculty Publications

Bifurcating electron transferring flavoproteins (Bf-ETFs) tune chemically identical flavins to two contrasting roles. To understand how, we used hybrid quantum mechanical molecular mechanical calculations to characterize noncovalent interactions applied to each flavin by the protein. Our computations replicated the differences between the reactivities of the flavins: the electron transferring flavin ( ETflavin) was calculated to stabilize anionic semiquinone (ASQ) as needed to execute its single-electron transfers, whereas the Bf flavin (Bfflavin) was found to disfavor the ASQ state more than does free flavin and to be less susceptible to reduction. The stability of ETflavin ASQ was attributed in part to …

Novel Isolation Method Reveals Sex-Specific Composition And Neurotoxicity Of Small Extracellular Vesicles In A Mouse Model Of Alzheimer’S Disease, Ahmed Elsherbini, Zhihui Zhu, Zainuddin Quadri, Simone M. Crivelli, Xiaojia Ren, Hemendra J. Vekaria, Priyanka Tripathi, Liping Zhang, Wenbo Zhi, Erhard Bieberich

Markey Cancer Center Faculty Publications

We developed a new method to isolate small extracellular vesicles (sEVs) from male and female wild-type and 5xFAD mouse brains to investigate the sex-specific functions of sEVs in Alzheimer’s disease (AD). A mass spectrometric analysis revealed that sEVs contained proteins critical for EV formation and Aβ. ExoView analysis showed that female mice contained more GFAP and Aβ-labeled sEVs, suggesting that a larger proportion of sEVs from the female brain is derived from astrocytes and/or more likely to bind to Aβ. Moreover, sEVs from female brains had more acid sphingomyelinase (ASM) and ceramide, an enzyme and its sphingolipid product important for …

The Kappa Opioid Receptor Agonist 16-Bromo Salvinorin A Has Anti-Cocaine Effects Without Significant Effects On Locomotion, Food Reward, Learning And Memory, Or Anxiety And Depressive-Like Behaviors, Ross Van De Wetering, Amy Ewald, Susan Welsh, Lindsay Kornberger, Samuel E. Williamson, Bryan D. Mcelroy, Eduardo R. Butelman, Thomas E. Prisinzano, Bronwyn M. Kivell

Markey Cancer Center Faculty Publications

Kappa opioid receptor (KOR) agonists have preclinical antipsychostimulant effects; however, adverse side effects have limited their therapeutic development. In this preclinical study, conducted in Sprague Dawley rats, B6-SJL mice, and non-human primates (NHPs), we evaluated the G-protein-biased analogue of salvinorin A (SalA), 16-bromo salvinorin A (16-BrSalA), for its anticocaine effects, side effects, and activation of cellular signaling pathways. 16-BrSalA dose-dependently decreased the cocaine-primed reinstatement of drug-seeking behavior in a KOR-dependent manner. It also decreased cocaine-induced hyperactivity, but had no effect on responding for cocaine on a progressive ratio schedule. Compared to SalA, 16-BrSalA had an improved side effect profile, with …

Recalcitrant Cutaneous Mastocytosis Treated With Genetically Informed Targeted Therapy: A Case Report, Laura Gleason, Volkan Tekmen, Alexa Cohen, Safiyyah Bhatti, Burcu Beksac, Jisun Cha, Pierluigi Porcu, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction:

Mastocytosis, a clonal proliferation of mast cells commonly involving the skin and bone marrow, has a varied clinical presentation ranging from cutaneous lesions to systemic disease. Cutaneous mastocytosis is managed symptomatically, but systemic mastocytosis is treated with targeted therapy against the mutated receptor tyrosine kinase c-KIT, the pathogenic driver of mastocytosis. However, there are no guidelines for the treatment of cutaneous mastocytosis refractory to symptomatic management.

We herein report a method to select genetically informed therapy for symptomatic and recalcitrant cutaneous mastocytosis.

Case presentation:

We performed a mutational analysis of dermal mast cells after enrichment by laser capture in …

Cost-Effective Microscopic Draping: Covid-19 Umbrella, Yusif Hajiyev, Ronald J Vilela

Faculty, Staff and Students Publications

We describe a cost-effective solution to limit aerosol transmission to the surgeon and other personnel in the operating room during otologic surgery.

Survival Of Middle Eastern And North African Individuals Diagnosed With Colorectal Cancer: A Population-Based Study In California, Timothy A Zaki, Argyrios Ziogas, Jenny Chang, Caitlin C Murphy, Hoda Anton-Culver

Faculty, Staff and Student Publications

BACKGROUND: Literature on colorectal cancer outcomes in individuals of Middle Eastern and North African (MENA) descent is limited. To address this gap, we estimated five-year colorectal cancer-specific survival by race and ethnicity, including MENA individuals, in a diverse, population-based sample in California.

METHODS: We identified adults (ages 18-79 years) diagnosed with a first or only colorectal cancer in 2004 to 2017 using the California Cancer Registry (CCR), including non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, Hispanic, and MENA individuals. For each racial/ethnic group, we calculated five-year colorectal cancer-specific survival and used Cox proportional hazards regression models to examine the association of …

Palliative Medicine Integration In The Usa: Cancer Centre Executives’ Attitudes, Joseph Chen, Allison De La Rosa, Dejian Lai, Rony Dev, Frances Lee Revere, David Lairson, Paige Wermuth, Eduardo Bruera, David Hui

Faculty, Staff and Student Publications

OBJECTIVES: To compare cancer centre (CC) executives' attitudes towards palliative care between National Cancer Institute-designated CCs (NCI-CCs) and non-NCI-designated CCs (non-NCI-CCs) in 2018 and to examine the changes in attitudes and beliefs between 2009 and 2018.

METHODS: CC chief executives at all NCI-CCs and a random sample of non-NCI-CCs were surveyed from April to August 2018. Twelve questions examined the executives' attitudes towards palliative care integration, perceived barriers and self-assessments. The primary outcome was agreement on the statement 'a stronger integration of palliative care services into oncology practice will benefit patients at my institution.' Survey findings from 2018 were compared …

A Review Of The Current State Of Global Surgical Oncology And The Role Of Surgeons Who Treat Cancer: Our Profession’S Imperative To Act Upon A Worldwide Crisis In Evolution, Aaron C. Saunders, Miriam Mutebi, T. Subramanyeshwar Rao

General Surgery, East Africa

Worldwide, the capacity of healthcare systems and physician workforce is woefully inadequate for the surgical treatment of cancer. With major projected increases in the global burden of neoplastic disease, this inadequacy is expected to worsen, and interventions to increase the workforce of surgeons who treat cancer and strengthen the necessary supporting infrastructure, equipment, staffing, financial and information systems are urgently called for to prevent this inadequacy from deepening. These efforts must also occur in the context of broader healthcare systems strengthening and cancer control plans, including prevention, screening, early detection, safe and effective treatment, surveillance, and palliation. The cost of …

Coffee Intake, Caffeine Metabolism Genotype, And Survival Among Men With Prostate Cancer, Justin R Gregg, Jeri Kim, Christopher Logothetis, Sam Hanash, Xiaotao Zhang, Ganiraju Manyam, Kenneth Muir, Graham G Giles, Janet L Stanford, Sonja I Berndt, Manolis Kogevinas, Hermann Brenner, Rosalind A Eeles, Practical Consortium, Peng Wei, Carrie R Daniel

Faculty, Staff and Student Publications

Background: Coffee intake may lower prostate cancer risk and progression, but postdiagnosis outcomes by caffeine metabolism genotype are not well characterized.

Objective: To evaluate associations between coffee intake, caffeine metabolism genotype, and survival in a large, multicenter study of men with prostate cancer.

Design, setting, and participants: Data from The PRACTICAL Consortium database for 5727 men with prostate cancer from seven US, Australian, and European studies were included. The cases included had data available for the CYP1A2 -163C>A rs762551 single-nucleotide variant associated with caffeine metabolism, coffee intake, and >6 mo of follow-up.

Outcome measurements and statistical analysis: Multivariable-adjusted Cox …

Microbiome Diversity In African American, European American, And Egyptian Colorectal Cancer Patients, Amr Elkholy, Nagavardhini Avuthu, Mohammed Abdalla, Michael Behring, Prachi Bajpai, Hyung-Gyoon Kim, Doaa Header, Reham Ah. Elwafa, Hesham Saed, Mansoor Saleh

Internal Medicine, East Africa

Purpose: Although there is an established role for microbiome dysbiosis in the pathobiology of colorectal cancer (CRC), CRC patients of various race/ethnicities demonstrate distinct clinical behaviors. Thus, we investigated microbiome dysbiosis in Egyptian, African American (AA), and European American (EA) CRC patients.

Patients and methods: CRCs and their corresponding normal tissues from Egyptian (n = 17) patients of the Alexandria University Hospital, Egypt, and tissues from AA (n = 18) and EA (n = 19) patients at the University of Alabama at Birmingham were collected. DNA was isolated from frozen tissues, and the microbiome composition was analyzed by 16S rRNA …

Leveraging A Surrogate Outcome To Improve Inference On A Partially Missing Target Outcome, Zachary R Mccaw, Sheila M Gaynor, Ryan Sun, Xihong Lin

Faculty, Staff and Student Publications

Sample sizes vary substantially across tissues in the Genotype-Tissue Expression (GTEx) project, where considerably fewer samples are available from certain inaccessible tissues, such as the substantia nigra (SSN), than from accessible tissues, such as blood. This severely limits power for identifying tissue-specific expression quantitative trait loci (eQTL) in undersampled tissues. Here we propose Surrogate Phenotype Regression Analysis (Spray) for leveraging information from a correlated surrogate outcome (eg, expression in blood) to improve inference on a partially missing target outcome (eg, expression in SSN). Rather than regarding the surrogate outcome as a proxy for the target outcome, Spray jointly models the …

Evolution Of Cisplatin Resistance Through Coordinated Metabolic Reprogramming Of The Cellular Reductive State, Wangie Yu, Yunyun Chen, Nagireddy Putluri, Abdullah Osman, Cristian Coarfa, Vasanta Putluri, Abu H M Kamal, Jennifer Kay Asmussen, Panagiotis Katsonis, Jeffrey N Myers, Stephen Y Lai, Wuhao Lu, Clifford C Stephan, Reid T Powell, Faye M Johnson, Heath D Skinner, Jawad Kazi, Kazi Mokim Ahmed, Linghao Hu, Addison Threet, Matthew D Meyer, James A Bankson, Tony Wang, Jack Davis, Kirby R Parker, Madison A Harris, Mokryun L Baek, Gloria V Echeverria, Xiaoli Qi, Jin Wang, Andy I Frederick, Alex J Walsh, Olivier Lichtarge, Mitchell J Frederick, Vlad C Sandulache

Faculty, Staff and Student Publications

BACKGROUND: Cisplatin (CDDP) is a mainstay treatment for advanced head and neck squamous cell carcinomas (HNSCC) despite a high frequency of innate and acquired resistance. We hypothesised that tumours acquire CDDP resistance through an enhanced reductive state dependent on metabolic rewiring.

METHODS: To validate this model and understand how an adaptive metabolic programme might be imprinted, we performed an integrated analysis of CDDP-resistant HNSCC clones from multiple genomic backgrounds by whole-exome sequencing, RNA-seq, mass spectrometry, steady state and flux metabolomics.

RESULTS: Inactivating KEAP1 mutations or reductions in KEAP1 RNA correlated with Nrf2 activation in CDDP-resistant cells, which functionally contributed to …

Does Proton Arc Therapy Has Potential Clinical Benefits For Hepatocellular Carcinoma?, Peilin Liu, R Dalfsen, M Soukup, Shupeng Chen, Lewei Zhao, Z Wang, X S. Gao, Thomas Quinn, Craig Stevens, Rohan Deraniyagala, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To investigate the potential clinical benefits and dose-averaged Linear Energy Transfer (LETd) sparing, utilizing proton arc plan for Hepatocellular carcinoma (HCC) patients in comparison with Intensity Modulated Proton Therapy (IMPT). Methods: Ten HCC patients have been retrospectively selected. Two planning groups were created: Proton Arc plans using Monaco ver. 6 and the clinical IMPT plan. Both planning groups used the same robustness parameters. The prescription dose is 67.5 Gy (RBE) in 15 fractions/ 66 GyE in 10 fractions of the Clinical Target Volume (CTV) following clinical IMPT plan. Robustness evaluations were performed to ensure target dose coverage. Normal Tissue …

Particle Arc Single-Isocenter Stereotactic Radiosurgery Of Multiple Brain Metastases, L Volz, S Mein, T Tessonnier, Peilin Liu, A Mairani, M Durante, Xuanfeng Ding, C Graeff, T Li

Conference Presentation Abstracts

Purpose: To develop spot-scanning proton (SPArc) and heavy ion (SHArc) arc therapy for single-isocenter stereotatic radiosurgery (SISRS) of multiple brain metastases (MBMs). First results achieved with dedicated planning infrastructure are compared to state-of-the -art volumetric modulated photon arc therapy (HA-VMAT). Methods: A multi-institutional collaboration was established to develop bespoke SPArc and SHArc SISRS infrastructure with available research and commercial treatment planning systems. Devised planning and delivery methods considered dedicated energy, spot, and multi-arc selection strategies. SPArc and SHArc (carbon and helium ions) plans were generated for MBM patients exhibiting 3-12 intracranial lesions with GTV volumes between 0.03ccm and 19.8ccm, at …

Divergent Clinical Presentations And Outcomes Among Children And Adolescents With Kaposi Sarcoma In Malawi And Tanzania, Liane R Campbell, Allison Silverstein, Erin Peckham-Gregory, William Kamiyango, Jimmy Villiera, Casey L Mcatee, Jason M Bacha, Carrie L Kovarik, Parth S Mehta, Toni Chanroo, Asulwisye Kapesa, Beatrice Malingoti, Rizine Mzikamanda, Nmazuo W Ozuah, Carl E Allen, Michael E Scheurer, Nader K El-Mallawany

Center for Medical Ethics and Health Policy Staff Publications

Objectives: The Kaposi sarcoma (KS) T0 versus T1 staging classification does not address the unique clinical features of paediatric KS in human gammaherpesvirus 8 (HHV-8) endemic regions of Africa. This study seeks to define patterns of childhood KS using a paediatric-specific approach.

Methods: The Lilongwe paediatric KS staging classification categorizes disease based on clinical phenotype: stage 1 = mild/moderate KS limited to cutaneous/oral involvement, stage 2 = primarily lymphadenopathic disease, stage 3 = woody edema KS, stage 4 = visceral and/or severe/disseminated mucocutaneous disease. Characteristics and outcomes were evaluated from paediatric referral centres in Lilongwe, Malawi, and Mbeya, Tanzania.

Results: …

A Novel Planning Framework For The Efficient Spot-Scanning Proton Arc Therapy Via The Particle Swarm Optimization (Sparc-Particle Swarm), Y Qian, R Dao, G Liu, Xiaoqiang Li, H Quan, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: The delivery efficiency is the bottleneck of spot-scanning proton arc therapy (SPArc) because of the numerous energy layers (EL) ascending switches. This study aims to develop a new algorithm to mitigate the need of EL ascending via water equivalent thickness (WET) sector selection followed by the particle swarm optimization (SPArc- particle swarm). Methods: SPArc- particle swarm divided the full arc trajectory into the optimal sectors based on the K-means clustering analysis of the relative mean WET. Within the sector, particle swarm optimization was used to minimize the total energy switch time, in which it optimized the energy selection integrated …

Oncolytic Dnx-2401 Virotherapy Plus Pembrolizumab In Recurrent Glioblastoma: A Phase 1/2 Trial, Farshad Nassiri, Vikas Patil, Leeor S Yefet, Olivia Singh, Jeff Liu, Rachel M A Dang, Takafumi N Yamaguchi, Mariza Daras, Timothy F Cloughesy, Howard Colman, Priya U Kumthekar, Clark C Chen, Robert Aiken, Morris D Groves, Shirley S Ong, Rohan Ramakrishna, Michael A Vogelbaum, Simon Khagi, Thomas Kaley, Jason M Melear, David M Peereboom, Analiz Rodriguez, Maxim Yankelevich, Suresh G Nair, Vinay K Puduvalli, Kenneth Aldape, Andrew Gao, Álvaro López-Janeiro, Carlos E De Andrea, Marta M Alonso, Paul Boutros, Joan Robbins, Warren P Mason, Adam M Sonabend, Roger Stupp, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F Lang, Gelareh Zadeh

Faculty, Staff and Student Publications

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response …

Metabolic Adaptation To Consume Butyrate Under Prolonged Resource Exhaustion, Sophia Katz, Claudia Grajeda-Iglesias, Bella Agranovich, Alia Ghrayeb, Ifat Abramovich, Sabrin Hilau, Eyal Gottlieb, Ruth Hershberg

Faculty, Staff and Student Publications

Bacteria must often survive following the exhaustion of their external growth resources. Fitting with this need, many bacterial species that cannot sporulate, can enter a state known as long term stationary phase (LTSP) in which they can persist for years within spent media. Several recent studies have revealed the dynamics of genetic adaptation of Escherichia coli under LTSP. Yet, the metabolic consequences of such genetic adaptation were not addressed. Here, we characterized the metabolic changes LTSP populations experience, over the first 32 days under LTSP. This allowed us to link genetic adaptations observed in a convergent manner across LTSP populations …

It Is Better To Light A Candle Than To Curse The Darkness: Single-Cell Transcriptomics Sheds New Light On Pancreas Biology And Disease, Amelia T Cephas, William L Hwang, Anirban Maitra, Oren Parnas, Kathleen E Delgiorno

Faculty, Staff and Student Publications

Recent advances in single-cell RNA sequencing and bioinformatics have drastically increased our ability to interrogate the cellular composition of traditionally difficult to study organs, such as the pancreas. With the advent of these technologies and approaches, the field has grown, in just a few years, from profiling pancreas disease states to identifying molecular mechanisms of therapy resistance in pancreatic ductal adenocarcinoma, a particularly deadly cancer. Single-cell transcriptomics and related spatial approaches have identified previously undescribed epithelial and stromal cell types and states, how these populations change with disease progression, and potential mechanisms of action which will serve as the basis …

Causal Linkage Of Presence Of Mutant Npm1 To Efficacy Of Novel Therapeutic Agents Against Aml Cells With Mutant Npm1, Christopher P Mill, Warren Fiskus, Kaberi Das, John A Davis, Christine E Birdwell, Tapan M Kadia, Courtney D Dinardo, Naval Daver, Koichi Takahashi, Koji Sasaki, Gerard M Mcgeehan, Xinjia Ruan, Xiaoping Su, Sanam Loghavi, Hagop Kantarjian, Kapil N Bhalla

Faculty, Staff and Student Publications

In AML with NPM1 mutation causing cytoplasmic dislocation of NPM1, treatments with Menin inhibitor (MI) and standard AML chemotherapy yield complete remissions. However, the causal and mechanistic linkage of mtNPM1 to the efficacy of these agents has not been definitively established. Utilizing CRISPR-Cas9 editing to knockout (KO) or knock-in a copy of mtNPM1 in AML cells, present studies demonstrate that KO of mtNPM1 from AML cells abrogates sensitivity to MI, selinexor (exportin-1 inhibitor), and cytarabine. Conversely, the knock-in of a copy of mtNPM1 markedly sensitized AML cells to treatment with MI or cytarabine. Following AML therapy, most elderly patients with …

National Institutes Of Health Diversity Supplement Awards: Experience Of Radiation Oncology Principal Investigators And Trainees, Afua A Yorke, Michael K Rooney, Jillian Rigert, Amy C Moreno, Clifton D Fuller, Eric C Ford

Faculty, Staff and Student Publications

No abstract provided.

Adaptive Immunity In Genitourinary Cancers, Madhuri Koti, Trinity Bivalacqua, Peter C Black, Toni Cathomen, Matthew D Galsky, James L Gulley, Molly A Ingersoll, Ashish M Kamat, Wassim Kassouf, D Robert Siemens, Jianjun Gao

Faculty, Staff and Student Publications

Context: While urothelial and renal cell cancers have exhibited modest responses to novel immune checkpoint inhibitors targeting the programmed death ligand 1 and its receptor, response rates in patients with prostate cancer have remained poor. The factors underlying suboptimal outcomes observed in patients treated with novel immunotherapies are still to be resolved.

Objective: To review the literature and describe the key adaptive immune physiological events associated with cancer progression and therapeutic response in genitourinary (GU) cancers.

Evidence acquisition: We performed a nonsystematic, collaborative narrative review to highlight recent advancements leading to the current state of knowledge on the critical mediators …

Cest-Mri For Body Oncologic Imaging: Are We There Yet?, Elena Vinogradov, Jochen Keupp, Ivan E Dimitrov, Stephen Seiler, Ivan Pedrosa

Faculty, Staff and Student Publications

Chemical exchange saturation transfer (CEST) MRI has gained recognition as a valuable addition to the molecular imaging and quantitative biomarker arsenal, especially for characterization of brain tumors. There is also increasing interest in the use of CEST-MRI for applications beyond the brain. However, its translation to body oncology applications lags behind those in neuro-oncology. The slower migration of CEST-MRI to non-neurologic applications reflects the technical challenges inherent to imaging of the torso. In this review, we discuss the application of CEST-MRI to oncologic conditions of the breast and torso (i.e., body imaging), emphasizing the challenges and potential solutions to address …

2021 Aapm Equity, Diversity, And Inclusion Climate Survey Executive Summary, Kristi R G Hendrickson, Stephen M Avery, Richard Castillo, Laura Cervino, Ashley Cetnar, Nolan L Gagne, Wendy Harris, Amirh Johnson, Megan E Lipford, Nadia Octave, Kelly C Paradis, Angélica Pérez-Andújar, Surendra Prajapati, Julianne Pollard-Larkin

Faculty, Staff and Student Publications

Purpose: The American Association of Physicists in Medicine (AAPM) shares the results, conclusions, and recommendations from the initial Equity, Diversity, and Inclusion Climate Survey conducted in 2021.

Methods and materials: The climate survey targeted medical physicists who are full members of the AAPM and included demographic inquiries and questions intended to assess the working environmental climate in terms of a sense of belonging and inclusion, experiences of discrimination and harassment, and obstacles to participation within the AAPM. The survey invitation was sent to 5,500 members. Responses were collected from 1385 members (response rate of 25%) between January and February 2021. …

Survival Outcomes Of Patients With Mycosis Fungoides Involving The External Ear And Ear Canal, Alex J Wilkinson, Marc-Elie Nader, Dianna Roberts, Madeleine Duvic, Jillian R Gunther, Bouthaina S Dabaja, Paul W Gidley

Faculty, Staff and Student Publications

OBJECTIVES/HYPOTHESIS: Mycosis Fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. Disease involvement of specific locations may be more significant than simply the symptoms associated with that site; it is possible that involvement of certain sites could be associated with poor prognosis. We aimed to evaluate the outcomes of patients with MF with documented involvement of the EAC and external ear.

STUDY DESIGN: Retrospective analysis.

METHODS: We retrospectively reviewed 40 patients with MF that were treated by otologists between 2012 and 2021.

RESULTS: We report the largest series of patients with MF involving the external ear and EAC. …

Redox-Dependent Activation Of Lung Epithelial Stat3 Is Required For Inducible Protection Against Bacterial Pneumonia, Vikram V Kulkarni, Yongxing Wang, Jezreel Pantaleon Garcia, Scott E Evans

Faculty, Staff and Student Publications

The lung epithelium is dynamic, capable of considerable structural and functional plasticity in response to pathogen challenges. Our laboratory has demonstrated that an inhaled combination of a Toll-like receptor (TLR) 2/6 agonist and a TLR9 agonist (Pam2ODN) results in robust protection against otherwise lethal pneumonias. We have previously shown that intact epithelial TLR signaling and generation of multisource epithelial reactive oxygen species (ROS) are required for inducible protection. Further investigating the mechanisms underlying this phenomenon of inducible resistance, reverse-phase protein array analysis demonstrated robust STAT3 (signal transducer and activator of transcription 3) phosphorylation following treatment of lung epithelial cells. We …

A 3d Perfusable Platform For In Vitro Culture Of Patient Derived Xenografts, Lindsey K Sablatura, Kristin M Bircsak, Peter Shepherd, Madhavi Bathina, Karla Queiroz, Mary C Farach-Carson, Rick A Kittles, Pamela E Constantinou, Anthony Saleh, Nora M Navone, Daniel A Harrington

Faculty, Staff and Student Publications

Many advanced cancer models, such as patient-derived xenografts (PDXs), offer significant benefits in their preservation of the native tumor's heterogeneity and susceptibility to treatments, but face significant barriers to use in their reliance on a rodent host for propagation and screening. PDXs remain difficult to implement in vitro, particularly in configurations that enable both detailed cellular analysis and high-throughput screening (HTS). Complex multilineage co-cultures with stromal fibroblasts, endothelium, and other cellular and structural components of the tumor microenvironment (TME) further complicate ex vivo implementation. Herein, the culture of multiple prostate cancer (PCa)-derived PDX models as 3D clusters within engineered biomimetic …

Author Correction: Comprehensive Molecular Characterization Of Mitochondrial Genomes In Human Cancers, Yuan Yuan, Young Seok Ju, Youngwook Kim, Jun Li, Yumeng Wang, Christopher J Yoon, Yang Yang, Inigo Martincorena, Chad J Creighton, John N Weinstein, Yanxun Xu, Leng Han, Hyung-Lae Kim, Hidewaki Nakagawa, Keunchil Park, Peter J Campbell, Han Liang

Faculty, Staff and Student Publications

No abstract provided.